TBDAS Linker

A Robust Linker for Solid Phase Diversity-Oriented Synthesis

The t-butyldiarylsilyl (TBDAS) linker was developed by Drs. Christine DiBlasi and Daniel Macks in our group for solid phase organic synthesis. This robust linker is stable to a variety of reaction conditions, but can be cleaved with relatively mild, chemoselective fluoride reagents to yield alcohol products.

As depicted graphically here, the TBDAS linker (blue) is stable to a range of acidic and basic reaction conditions commonly used in organic synthesis. In contrast, previously reported aryl­diisopropyl­silyl (ArDIPS, red) and alkyl­diisopropyl­silyl (AlkylDIPS) linkers are generally less stable to these conditions.

The TBDAS linker is activated by chlorination with dichoro­dimethyl­hydantoin, followed by loading of the desired alcohol-containing substrate. After synthetic transformation, the product is cleaved from the solid support by treatment with TBAF, TAS-F, or HF·pyr. The product can be conveniently separated from the cleavage reagents by passage through a short plug of reverse phase over normal phase silica gel.